Synthesis method of 1H-imidazole-4-carboxylic acid

Abstract

The invention discloses a synthesis method of 1H-imidazole-4-carboxylic acid. The method comprises steps as follows: (1) a hydrochloric acid solution is added to a reaction kettle, chromium trioxide is added under the stirring condition, the mixture is stirred uniformly and heated to 40-50 DEG C, pyridine is dropwise added, the mixture is stirred to react for 2-3 h after pyridine is dropwise added, PCC (pyridinium chlorochromate) is prepared, TiO2 is added, a dichloromethane solution of 4-methylimidazole is dropwise added under the stirring condition, the mixture is subjected to a reaction at40-50 DEG C for 3-4 h, then, filtration and centrifugation are performed, an organic layer is collected, reduced pressure distillation is performed, and 1H-imidazole-4-formaldehyde is prepared; (2) prepared 1H-imidazole-4-formaldehyde and dichloromethane are mixed, the obtained mixture is heated to 40-50 DEG C, KMnO4 is added, the mixture is mixed uniformly and stirred for a reaction for 3-4 h, filtration, reduced pressure distillation and recrystallization are performed, and 1H-imidazole-4-carboxylic acid is prepared. The synthesis method is simple to operate and mild in condition, fewer by-products are produced, the product purity is high and the product yield is higher.

Description

technical field [0001] The invention relates to the field of pharmaceutical intermediates, in particular to a method for synthesizing 1H-imidazole-4-carboxylic acid. Background technique [0002] Imidazole compounds are a class of five-membered rings with 1,3-two nitrogen heteroatoms, which can be regarded as heterocyclic compounds in which a methine group on the pyrrole ring is replaced by a tertiary amine nitrogen. Imidazole is a planar molecule with a nearly regular pentagonal shape. The ring has a ring-shaped closed conjugated system with (4n+2) π electrons, so it has certain aromaticity. At the same time, imidazole is a heterocyclic ring rich in π electrons. The 6 electrons are distributed over 5 atoms, mainly concentrated on the nitrogen atom. [0003] Imidazole compounds widely exist in alkaloids and amino acids in the human body, and are important structural units in the human body. In the human body, it mainly exists in histidine, which has an important impact on ...

AI Technical Summary

Problems solved by technology

The synthetic method of the 1H-imidazole-4-formic acid of relevant research report at present comprises: (1) take 4-methylimidazole as raw material, under high pressure condition, with cobalt acetate, manganese acetate and sodium bromide as catalyst, methyl Oxidation to carboxyl, the method catalyst is relatively expensive, and the operation process has potential safety hazards; (2) use benzimidazole or imidazole as raw material to prepare imidazole-4,5-dicarboxylic acid, and then carry out decarboxylation treatment to obtain the target product. The reaction time is longer, the post-processing is more cumbersome, and it is difficult to industrialize production